Rapid purification of small molecule libraries by ion exchange chromatography

Tetrahedron Letters

Volumn 38, Issue 19, 1997, Pages 3357-3360

  Siegel, Miles G ^a   Hahn, Patric J ^a   Dressman, Bruce A ^a   Fritz, James E ^a   Grunwell, Jocelyn R ^a   Kaldor, Stephen W ^a  

^a ELI LILLY AND COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINE;

ARTICLE; AUTOMATION; DRUG PURIFICATION; DRUG SYNTHESIS; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; IN VITRO STUDY; ION EXCHANGE CHROMATOGRAPHY; TECHNIQUE;

EID: 0030998777     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(97)00650-3     Document Type: Article

References (18)

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2. Kobayashi, S.; Nagayama, S. J. Am. Chem. Soc. 1996, 118, 8977-8978.
3. Parlow, J. J. Tetrahedron Lett. 1996, 37, 5257-5260.
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5. Studer, A.; Hadida, S.; Ferritto, R.; Kim, S. Y.; Jeger, P.; Wipf, P.; Curran, D. P. Science 1997, 275, 823-826.
6. Kaldor, S. W.; Siegel, M. G.; Fritz, J. E.; Dressman, B. A.; Hahn, P. J. Tetrahedron Lett. 1996, 37, 7193-7196.
7. Dorfner, K. Ion Exchangers: Properties and Applications, 3rd ed.; Ann Arbor Science Publishers, inc.: Ann Arbor, MI, 1972.
8. Wolniwiecz, E. Textilindustrie 1964, 66, 746.
9. Yamamoto, S.; Nakanishi, K.; Matsuno, R. Ion-Exchange Chromatography of Proteins; Marcel Dekker, Inc.: New York, 1988; Vol. 43.
10. Kaye, B.; Herron, W. J.; Macrae, P. V.; Robinson, S.; Stopher, D. A.; Venn, R. F.; Wild, W. Anal. Chem. 1996, 68, 1658-1660.
11. Some workers have explored the use of ion exchange resins in the production of combinatorial libraries; see Gayo, L. M.; Suto, M. J. Tetrahedron Lett. 1997, 38, 513-516; Parlow, J. J. Tetrahedron Lett. 1996, 37, 5257-5260; Lawrence, R. M.; Biller, S. A.; Fryszman, O. M.; Poss, M. A.; Weller, H. A. A Simple Procedure for the Automated Solution Phase Synthesis and Purification of Non-Peptidic Amides. In Conference on Molecular Diversity and Combinatorial Chemistry; January 28,1996: San Diego, CA, 1996.
12. Some workers have explored the use of ion exchange resins in the production of combinatorial libraries; see Gayo, L. M.; Suto, M. J. Tetrahedron Lett. 1997, 38, 513-516; Parlow, J. J. Tetrahedron Lett. 1996, 37, 5257-5260; Lawrence, R. M.; Biller, S. A.; Fryszman, O. M.; Poss, M. A.; Weller, H. A. A Simple Procedure for the Automated Solution Phase Synthesis and Purification of Non-Peptidic Amides. In Conference on Molecular Diversity and Combinatorial Chemistry; January 28,1996: San Diego, CA, 1996.
13. Some workers have explored the use of ion exchange resins in the production of combinatorial libraries; see Gayo, L. M.; Suto, M. J. Tetrahedron Lett. 1997, 38, 513-516; Parlow, J. J. Tetrahedron Lett. 1996, 37, 5257-5260; Lawrence, R. M.; Biller, S. A.; Fryszman, O. M.; Poss, M. A.; Weller, H. A. A Simple Procedure for the Automated Solution Phase Synthesis and Purification of Non-Peptidic Amides. In Conference on Molecular Diversity and Combinatorial Chemistry; January 28,1996: San Diego, CA, 1996.
14. For a recent and somewhat novel example of the use of solid phase extraction in the purification of combinatorial libraries, see: Virgilio, A. A.; Schürer, S. C.; Ellman, J. A. Tetrahedron Lett. 1996, 37, 6961-6964.
15. Varian SCX columns are sulfonic acid residues covalently linked to silica gel. These prepacked columns are particularly convenient in that they readily fit off the shelf automated solid phase extraction equipment.
16. 4OD): 7.1-7.3 (m, 7H); 6.84 (d, 2H, J=9 Hz); 3.81 (s, 3H); 3.50 (t, 2H, J=6.8 Hz); 2.83 (t, 2H, J=6.8 Hz). MS (M+l): 271.1.
17. We have found it necessary to purify commercially available 1-(2-hydroxyphenyl)piperazine by flash chromatography in order to achieve optimal results
18. All compounds gave mass spectral data consistent with the desired structure.